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Objectives: Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) is a potential diagnostic tool for lymph node assessment in patients with head and neck cancer. Validation by radiologic-pathologic correlation is essential before the method is evaluated in clinical studies. In this study, MRI signal intensity patterns of lymph nodes are correlated to their histopathology to develop a new USPIO-enhanced MRI reading algorithm that can be used for nodal assessment in head and neck cancer patients. Materials and Methods: Ten head and neck cancer patients underwent in vivo USPIO-enhanced MRI before neck dissection. An ex vivo MRI of the neck dissection specimen was performed for precise coregistration of in vivo MRI with histopathology. Normal clinical histopathological workup was extended with meticulous matching of all lymph nodes regarded as potentially metastatic based on their in vivo MRI signal intensity pattern. On the basis of histopathology of resected nodes, in vivo MRI signal characteristics were defined separating benign from malignant lymph nodes. Results: Fifteen of 34 node-to-node correlated lymph nodes with remaining signal intensity on T2*-weighted MRI were histopathologically metastatic and 19 were benign. Radiological analysis revealed that metastatic lymph nodes showed equal or higher MRI signal intensity when compared with lipid tissue on T2*-weighted MGRE sequence (15/16 lymph nodes; 94%), whereas healthy lymph nodes showed lower (17/19 lymph nodes; 89%) or complete attenuation of signal intensity (273/279; 98%) when compared with lipid tissue on T2*-weighted MGRE. Histopathology of all resected specimens identified 392 lymph nodes. Six lymph nodes with (micro)metastases were missed with in vivo MRI. Whether these 6 lymph nodes were correlated to a nonmalignant lymph node on in vivo MRI or could not be detected at all is unclear. Conclusions:We developed a new reading algorithm to differentiate benign from malignant lymph nodes in head and neck cancer patients on the basis of their appearance on high-resolution T2*-weighted USPIO-enhanced MRI. Next steps involve validation of our reading algorithm to further improve the accuracy of neck lymph node staging with USPIO-enhanced MRI in prospective clinical studies with larger number of patients.

In head and neck cancer, the presence of nodal disease is a strong determinant of prognosis and treatment. Despite the use of modern multimodality diagnostic imaging, the prevalence of occult nodal metastases is relatively high. This is why in clinically node negative head and neck cancer the lymphatics are treated “electively” to eradicate subclinical tumor deposits. As a consequence, many true node negative patients undergo surgery or irradiation of the neck and suffer from the associated and unnecessary early and long-term morbidity. Safely tailoring head and neck cancer treatment to individual patients requires a more accurate pre-treatment assessment of nodal status. In this review, we discuss the potential of several innovative diagnostic approaches to guide customized management of the clinically negative neck in head and neck cancer patients.

Background: In various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation. Here, a workflow is presented, which is designed to compare MRI-visible lymph nodes on a node-to-node basis with histopathology. Methods: In patients with prostate, rectal, periampullary, esophageal, and head-and-neck cancer, in vivo USPIO-enhanced MRI was performed to detect lymph nodes suspicious of harboring metastases. After lymphadenectomy, but before histopathological assessment, a 7 Tesla preclinical ex vivo MRI of the surgical specimen was performed, and in vivo MR images were radiologically matched to ex vivo MR images. Lymph nodes were annotated on the ex vivo MRI for an MR-guided pathological examination of the specimens. Results: Matching lymph nodes of ex vivo MRI to pathology was feasible in all cancer types. The annotated ex vivo MR images enabled a comparison between USPIO-enhanced in vivo MRI and histopathology, which allowed for analyses on a nodal, or at least on a nodal station, basis. Conclusions: A workflow was developed to validate in vivo USPIO-enhanced MRI with histopathology. Guiding the pathologist towards lymph nodes in the resection specimens during histopathological work-up allowed for the analysis at a nodal basis, or at least nodal station basis, of in vivo suspicious lymph nodes with corresponding histopathology, providing direct information for validation of in vivo USPIO-enhanced, MRI-detected lymph nodes.

Background: The aim of this study was to investigate the feasibility of flexible endoscopy-guided tracer injection for sentinel lymph node (SLN) identification in patients with laryngeal and pharyngeal carcinoma. Methods: Sixteen cT1-4N0-2M0 patients with laryngeal or pharyngeal carcinoma underwent intra-and peritumoral [ 99m Tc]Tc-nanocolloid injections after topical anesthesia under endoscopic guidance. SPECT-CT scans were performed at two time points.Results: Tracer injection and visualization of SLNs was successful in 15/16 (94%) patients. Median number of tracer injections was 1 intratumoral and 3 peritumoral. The median duration of the endoscopic procedure including tracer injection after biopsy taking was 7 min (range 4-16 min). A total of 28 SLNs were identified which were all visualized on the early and late SPECT-CT. Most SLNs were visualized in neck levels II and III. Conclusions: Flexible endoscopy-guided tracer injection for SLN identification is a feasible and fast procedure in laryngeal and pharyngeal carcinoma patients.